We propose new approaches to establishing molecular correlates of functional and structural features of mammalian dorsal root ganglion and hippocampal neurons. The focus will be upon a) neurons of these two populations that employ multiple synaptic mediators, and b) the manner in which key molecular determinants are modulated. The specific aims are: 1) to determine molecular features of primary afferent and hippocampal neurons that distinguish between functional and/or morphological subclasses; 2) to determine the parts played by peptides and other chemical mediators in the function of primary afferent and hippocampal neurons; 3) to examine the biochemical mechanisms underlying modulation of membrane receptors and channels, and the possible coupling of such events to expression of neuron-specific molecular determinants. The experiments will be done in vivo, in cultures of the dorsal root ganglia and hippocampal neurons and in hippocampal slices. Established morphological (light and electron microscopic) and electrophysiological (microelectrode and patch clamp) techniques are to be coupled with immunocytochemical, biochemical, pharmacological and molecular genetic approaches. A facility for the generation of specific polyclonal and monoclonal antibodies and for in situ hybridization histochemistry will be set up for common use by the four projects.